Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Homozygous loss of alleles of the retinoblastoma susceptibility locus (RB1) has been implicated in the onset of many different solid tumors. Heterozygous deletions of chromosome 13q14, the region containing the RB1 locus, have been observed by us in several subvariants of leukemia and preleukemia. We examined four cases of leukemia and one case of preleukemia for homozygous inactivation of the RB1 locus; in at least one case, evidence supports the concept that homozygous loss of both alleles of RB1 was an important step during leukemogenesis.
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PMID:Structural alterations at the putative retinoblastoma locus in some human leukemias and preleukemia. 239 69

Human leukemia cell lines were examined for the status of the retinoblastoma (RB) protein by immunoblotting analysis using antibodies raised against the TrpE-RB fusion protein. One of 16 cell lines examined, the T-cell acute lymphoblastic leukemia (ALL) line HSB-2, lacked the 110-Kd RB protein. Southern blot analysis of genomic DNA extracted from HSB-2 cells showed a large homozygous deletion of the RB gene, stretching from exon 18 beyond exon 27. Northern blot analysis showed multiple, abnormal RB transcripts in HSB-2. A truncated protein (72 Kd) was detected with 35S-methionine labeling but not with 32P-orthophosphate labeling of the HSB-2 cells. The genomic deletion of greater than 85 kb DNA at the RB locus (13q14) was not detectable in the karyotype of the HSB-2 cells. Among the 16 human leukemia cell lines examined for the status of the RB gene, only one, the HSB-2 line, showed an abnormal RB protein. Further study of primary leukemia and lymphoma samples appears to be warranted.
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PMID:Homozygous deletion of the retinoblastoma gene in an acute lymphoblastic leukemia (T) cell line. 240 25

Data from the Papua New Guinea Tumour Registry and the Central Pathology Department were reviewed in order to document the incidence and pattern of malignancies in children in Papua New Guinea. Altogether, 680 cases of histologically defined childhood malignancies were recorded during the 14.5 years from 1971 to 1985. The frequencies of the various tumours were compared with past data and with published data from other countries. The incidence of malignancies in Papua New Guinean children appeared to be low, 36.5/1,000,000/year, with a male:female ratio of 1.6:1. Lymphoma was the most commonly occurring tumour and Burkitt's tumour accounted for 53% in this group. The relative frequency of leukaemia compared with lymphoma appeared to have increased since a previous report. A relatively high incidence of retinoblastoma (6.9%) and of other embryonal tumours (4.8%) was recorded, whilst the recorded incidences of tumours of the central nervous system (3.8%) and neuroblastoma (3.7%) were low. Ewing's sarcoma accounted for almost half of the bone tumours, whilst Kaposi's sarcoma was a relatively frequent soft tissue tumour. Differences and similarities between the Papua New Guinea data and those from other countries are discussed.
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PMID:Childhood malignant tumours in Papua New Guinea. 246 3

Introduction of an exogenous retinoblastoma (RB) gene in RB-deficient retinoblastoma or osteosarcoma cells has been shown to suppress their neoplastic phenotype. In experiments designed to explore the potential mechanism of RB tumor suppression, we report here that the phosphorylation state of RB protein is modulated during normal cellular events. In resting cells, RB protein is present in its least phosphorylated form; in rapidly proliferating cells, RB protein is highly phosphorylated. Maximal phosphorylation is associated with S phase of the cell cycle. Induction of differentiation in several human leukemia cell lines by treatment with phorbol ester or retinoic acid leads to dephosphorylation of RB. Time course studies indicate that RB dephosphorylation precedes the total arrest of cell growth during differentiation. These observations strongly suggest that the function of RB protein is modulated by a phosphorylation/dephosphorylation mechanism during cell proliferation and differentiation.
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PMID:Phosphorylation of the retinoblastoma gene product is modulated during the cell cycle and cellular differentiation. 267 46

The present investigation demonstrates that leukoregulin, a cytokine secreted by natural killer (NK) lymphocytes up-regulates the sensitivity of tumor cells to lymphokine-activated killer (LAK) cell cytotoxicity. It has been previously established that leukoregulin increases the sensitivity of sarcoma, carcinoma and leukemia cells to natural killer (NK) cell cytotoxicity. Tumor cells were treated with leukoregulin for 1 h at 37 degrees C and tested for sensitivity to NK and LAK cytotoxicity in a 4-h chromium-release assay. NK-resistant Daudi, QGU and C4-1 human cervical carcinoma cells became sensitive to NK cytotoxicity after leukoregulin treatment, and their sensitivity to LAK was increased two- to sixfold. Y-79 retinoblastoma cells, which are moderately sensitive to NK and very sensitive to LAK, became increasingly sensitive (two- to four-fold) to both NK and LAK cell cytotoxicity. Recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF), recombinant interleukin-1 (alpha and beta), recombinant interferon gamma, recombinant tumor necrosis factor or combinations of the latter two failed to up-regulate tumor cell sensitivity to NK and LAK cell cytotoxicity. However, treatment with recombinant interferon gamma for 16-18 h, GM-CSF and interleukin-1 beta for 1 h induced a state of target cell resistance to both NK and LAK cell cytotoxicity. Leukoregulin may have an important physiological function in modulating NK and LAK cell cytotoxicity by increasing the sensitivity of target cells to these natural cellular immunocytotoxicity mechanisms.
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PMID:Leukoregulin up-regulation of tumor cell sensitivity to natural killer and lymphokine-activated killer cell cytotoxicity. 268 71

The occurrence of cancer among the 1,348 offspring of 2,441 survivors of childhood cancer, treated before 1978, was investigated. Information was obtained through a questionnaire sent to the general practitioners of these survivors. Twenty-three of 52 offspring born to survivors of heritable retinoblastoma developed retinoblastoma; the heritable form of retinoblastoma is known to be transmitted to offspring as an autosomal dominant. None of the 94 offspring born to the 54 survivors of unilateral retinoblastoma with no family history of the disease have developed the disease. This implies that it is unlikely that more than 9% of survivors of unilateral retinoblastoma with no family history have the germ-cell mutation; consequently it is unlikely that more than 4% of their offspring will be affected. Among the 1,199 offspring born to 629 survivors of other childhood malignant disease, who produced children, one acute monocytic leukaemia and one acute lymphoblastic leukaemia were observed. This is more than expected on the basis of the general population (one-tailed p = 0.04). However, the types of cancer observed in these 2 offspring and their parents conform to a previously described familial aggregation of cancers. Only a small number of children were born to survivors who received therapy that was potentially germ-cell mutagenic, and thus it is not possible to make any accurate estimation of their risk of malignant disease.
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PMID:Cancer among 1,348 offspring of survivors of childhood cancer. 273 8

Of the 1,310 bone marrow examinations performed in a 16-month period in patients with diverse haematological, oncological and other disorders, 620 had sufficient data for analysis. Seventy-nine percent were from the two main hospitals viz: Parirenyatwa and Harare Central Hospitals. Investigation for anaemia (42.6 percent), staging of malignant disease (14.4 percent) and pancytopenia (10.3 percent) formed the commonest triad of indications for requesting the examination. There were 318 (51 percent) males, mean age +/- s.d. of 33.8 +/- 22.6 years (range 6 months to 80 years); and 302 (49 percent) females, mean age +/- s.d. of 32.6 +/- 20.7 years (range 6 months to 78 years) giving a male to female ratio of 1.1:1. Of the 620 patients studied, 452 (73 percent) were adults (M:F ratio of 1:1) mean age +/- s.d. of 42.8 +/- 17.3 years (range 16-80 years); and 168 (27 percent) were children (M:F ratio of 1.1:1) mean age +/- s.d. of 7.3 +/- 4.5 years (range 6 months to 15 years). The three commonest diseases in the combined (adults and children) group were: megaloblastic anaemia (25.2 percent); acute or chronic leukaemia (19.2 percent) and iron deficiency anaemia (10.5 percent). These three diseases respectively accounted for 32 percent, 17.5 percent and 10.8 percent of the cases in the adult (16 years and over) group; whereas in the paediatric (0-15 years) group, the top three diseases were: acute leukaemia (22 percent); Hodgkins and non-Hodgkins lymphomas (14.3 percent) and retinoblastoma (13.7 percent). These preliminary observations indicate some of the commonest haematological and oncological disorders where intense research might be beneficial to the community in Zimbabwe.
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PMID:A prospective analysis of 620 bone marrow examinations in Zimbabwe: preliminary observations. 277 9

Among a cohort of 10,106 three-year survivors of childhood cancer, 90 second primary tumours (SPTs) were observed. Within 25 years of 3-year survival about 4% developed a SPT, about 6-fold expected, the relative risk not varying much with increasing follow-up. Following genetic retinoblastoma we observed 30-fold the expected number of SPTs, and over 400-fold the expected number of osteosarcomas. The risk of SPT in the absence of radiotherapy and chemotherapy (inherent risk) following genetic retinoblastoma was 13-fold expected and over 200-fold the expected number of osteosarcomas were observed. There was evidence that both radiotherapy and cyclophosphamide were associated with an increased risk of SPT. After all first primary tumours (FPTs) excluding retinoblastoma we observed almost 5-fold the expected number of SPTs. The inherent risk was 4-fold expected, the relative risks associated with radiotherapy but no chemotherapy, and both radiotherapy and chemotherapy were 6- and 9-fold expected respectively. There were about 20-fold the number of malignant bone tumours expected, most were osteosarcoma; also 7-fold the number of central nervous system tumours expected. There were 8 basal cell carcinomas and it seems likely that radiotherapy was involved in the development of some of these. Radiotherapy appears to have been involved in the development of many of the SPTs observed following all FPTs excluding retinoblastoma, particularly after CNS tumours, Wilms' tumour and Hodgkin's disease. Currently there is insufficient follow-up to examine the risk following chemotherapy. After acute leukaemia there was 20-fold the expected number of central nervous system tumours, though this is based on only 3 cases; whether therapy is directly involved in their development is uncertain. The risks we report are rarely greater than those reported in previous large-scale studies; in most instances they are substantially less. It is very unlikely that many SPTs were missed with our follow-up system so alternative explanations require further investigation; in particular it is possible the lower risks in our data compared to series treated in the United States may be explained, in part, by less combination therapy and lower doses of radiotherapy.
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PMID:Incidence of second primary tumours among childhood cancer survivors. 282 73

The authors have studied the different situations that prompt a request for genetic counseling if different members of the same family suffer from cancer. Six possibilities are considered: the cancer concerned is a genetic disease per se (e.g. retinoblastoma, thyroid cancer with amyloid stroma); the genetic disease is often complicated with cancer (e.g. intestinal polyposis); the genetic disease is occasionally complicated with cancer (e.g. neurofibromatosis); cancer is part and parcel of the genetic disease (e.g. chromosomal abnormalities); in addition, there are two special situations: "cancer-prone families" and families who request genetic counseling after one single case (e.g. cancer of leukaemia in a child).
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PMID:[Genetic counseling in cancerology]. 295 Apr 12

Altered structure and regulation of the c-myc proto-oncogene have been associated with a variety of human tumours and derivative cell lines, including Burkitt's lymphoma, promyelocytic leukaemia and small cell lung cancer (SCLC). The N-myc gene, first detected by its homology to the second exon of the c-myc gene, is amplified and/or expressed in tumours or cell lines derived from neuroblastoma, retinoblastoma and SCLC. Here we describe a third myc-related gene (L-myc) cloned from SCLC DNA with homology to a small region of both the c-myc and N-myc genes. Human genomic DNA shows an EcoRI restriction fragment length polymorphism (RFLP) of L-myc defined by two alleles (10.0- and 6.6-kilobase (kb) EcoRI fragments), neither associated disproportionately with SCLC. Mouse and hamster DNAs exhibit a 12-kb EcoRI L-myc homologue, which indicates conservation of the gene in mammals. Gene mapping studies assign L-myc to human chromosome region 1p32, a location distinct from that of either c-myc or N-myc but associated with cytogenetic abnormalities in certain human tumours. This L-myc sequence is amplified 10-20-fold in four SCLC cell line DNAs and in one SCLC tumour specimen taken directly from a patient. Either the 10.0- or 6.6-kb allele can be amplified and in heterozygotes only one of the two alleles was amplified in any SCLC genome. SCLC cell lines with amplified L-myc sequences express L-myc-derived transcripts not seen in SCLC with amplified c-myc or N-myc genes. In addition, some SCLCs without amplification also express L-myc-related transcripts. Together, these findings suggest an enlarging role for myc-related genes in human lung cancer and provide evidence for the concept of a myc family of proto-oncogenes.
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PMID:L-myc, a new myc-related gene amplified and expressed in human small cell lung cancer. 299 22


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